Evaluation of interleukin-9 expression as a potential therapeutic target in chronic lymphocytic leukemia in a cohort of Egyptian patients

Background: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that has a highly variable clinical course. Genomic features as zeta-chain-associated protein kinase 70 (ZAP70) expression and CD38 expression provide further differentiation of disease prognosis. Extensive studies have confirmed the oncogenic activities of IL-9 in lymphoma. The aim of the current study was to investigate the contribution of IL-9 expression to the pathogenesis of CLL and its correlation to other prognostic parameters.Methods: This study was conducted on 80 patients at diagnosis with CLL and 80 healthy controls. Using real time polymerase chain reaction and enzyme linked immunosorbant assay, IL-9 mRNA expression and its serum level were compared between patients and controls. They were both correlated with other prognostic factors.Results: There was an overexpression of IL-9 in CLL patients that correlated with modified Rai staging, ZAP70, CD38 and all hallmarks of an active and aggressive disease. The correlation between IL-9 upregulation and patient characteristics provided a direct clinical evidence for its contribution to the pathogenesis of CLL.Conclusions: Significantly higher expression of IL -9 measured at both the mRNA and the protein levels in patients with CLL that correlates with more complex course of the disease and worse prognosis may allow one to speculate its importance in the pathogenesis of the disease and its possible role as a potential therapeutic target

BONE MINERAL DENSITY AND VITAMIN D RECEPTOR GENETIC VARIANTS IN EGYPTIAN CHILDREN WITH BETA THALASSEMIA ON VITAMIN D SUPPLEMENTATION

Background: Low bone mineral density (BMD) is a characteristic feature of Beta thalassemia major (βTM) patients. Vitamin D is important for bone mineralization. Vitamin D receptors (VDR) genetic variants may be related to vitamin D status and BMD. Objectives:  To evaluate the effect of VDR genetic variants on vitamin D levels and BMD in βTM Egyptian patients supplemented with vitamin D. Methods: This study was conducted on forty children with βTM and forty unrelated healthy sex and age-matched controls. Serum calcium, phosphorus, ALP, ferritin and vitamin D were measured. VDR genetic variants (BsmI, TaqI, and FokI) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD was measured by dual-energy X-ray densitometry (DEXA) of the lumbar spine. Results: In βTM patients, 22.5% had deficient, 50% had insufficient and only 27.5% had sufficient levels of vitamin D. BMD Z score was significantly lower in βTM patients compared to controls (p<0.001). Osteopenia and osteoporosis of lumbar spines were observed in 70% and 22.5% of βTM patients respectively. BsmI bb and FokI Ff and ff genotypic variants were significantly associated with lower vitamin D and BMD Z score. No association was observed with TaqI genotypic variants. Conclusions: We reported a high prevalence of low BMD in βTM despite vitamin D supplementation. The BsmI bb, FokI Ff and ff genotypic variants of VDR can be considered as risk factors for the occurrence of osteoporosis in these children. Vitamin D doses should be adjusted individually according to the genetic makeup of each patient

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Dentoskeletal effects of the forsusTM fatigue resistance device in the treatment of class II malocclusion: A systematic review and meta-analysis

OBJECTIVE: The aim of this systematic review and meta-analysis is to quantitatively compare previous studies that evaluated skeletal and dentoalveolar effects of the ForsusTM Fatigue Resistance Device (FRD) in the treatment of Class II malocclusion with a matched untreated control group. MATERIALS AND METHODS: Four electronic searches PubMed, Web of Science, Cochrane Library, and Science Direct that were limited to articles on human studies comparing the effect of Forsus appliance with a matched control group in the treatment of Class II malocclusion from the year (2000–2017). An additional manual search was carried out by examining the references of the included articles, SEARCH terms included; Forsus and Class II malocclusion. The quality of the included studies was assessed using the modified methodological score for clinical trials. The data were analyzed using Michael Borenstein's Comprehensive Meta-Analysis Software (V3.3.070, Biostat, Inc., US). RESULTS: Seven studies were included comprising 273 participants (Forsus group = 142; control group = 131). The results indicated a statistical significant skeletal effect of the Forsus appliance on increasing the occlusal plane only (P < 0.001). The results also indicated a statistical significant (P < 0.001) dentoalveolar effects of the Forsus appliance on the following outcomes; protruding, proclining, and intruding lower incisors; retroclining upper incisors, distalizing and intruding upper molars, as well as reducing overjet and overbite. CONCLUSIONS: The ForsusTM showed positive effects on the maxillary incisors and first molars as well as overjet and overbite. However, multiple negative effects were reported on the occlusal plane and lower incisors that need to be considered when using such appliance in treating Class II malocclusion

Comparison of shear bond strength to clinically simulated debonding of orthodontic brackets: An in vitro study

Objectives: To assess in vitro the quantitative and qualitative debonding behavior of the AEZ debonding plier, compared to shear debonding force, in debonding orthodontic metal brackets. Materials and Methods: Thirty-two extracted premolars bonded with metal brackets were randomly divided into two equal groups according to the type of simulated debonding method; compressive bond strength (CBS) group using AEZ debonding plier (Ormco Corporation, USA) attached to the Instron machine, and shear bond strength (SBS) group using regular Instron attachments. All teeth were subjected to debonding forces, and debonding strength was assessed. The buccal surfaces were then examined, under a stereomicroscope, and adhesive remnants were scored using adhesive remnant index (ARI). Debonding strengths comparison was performed using the independent sample t-test. ARI score comparison was performed using the Mann-Whitney U-test. Correlation between debonding strength and ARI scores was performed using the Spearman correlation. Results: There was no significant difference in mean debonding strength between the SBS (M = 6.17 ± 0.77 MPa) and CBS (M = 6.68 ± 1.67 MPa) groups (P > 0.05). The CBS group showed significantly less adhesive remnants than the SBS group (P < 0.05); 62.5% of CBS group had ARI score 1, whereas 68.8% of SBS group had ARI score 3. No significant correlation between ARI and debonding strength was found (P < 0.05). Conclusion: SBS was found to produce similar debonding strength to the AEZ debonding plier in vitro. However, the AEZ debonding plier resulted in less adhesive remnant which is of great advantage for reducing chair-time during cleanup after debonding brackets

Zinc Ameliorate Oxidative Stress and Hormonal Disturbance Induced by Methomyl, Abamectin, and Their Mixture in Male Rats

Exposure to mixtures of toxicants (e.g., pesticides) is common in real life and a subject of current concern. The present investigation was undertaken to assess some toxicological effects in male rats following exposure to methomyl (MET), abamectin (ABM), and their combination (MET+ABM), and to evaluate the ameliorative effect of zinc co-administration. Three groups of rats were designated for MET, ABM, and the mixture treatments. Three other groups were designated for zinc in conjunction with the pesticides. Additionally, one group received water only (control), and the other represented a positive zinc treatment. The obtained results revealed that MET was acutely more toxic than ABM. The tested pesticides induced significant elevation in lipid peroxidation and catalase levels, while declined the levels of the other tested parameters e.g., Superoxide dismutase (SOD), Glutathione-S-transferase (GST), Glutathione peroxidase (GPx), Glutathione reductase (GR), Cytochrome P450 (CYP450), testosterone, and thyroxine). Biochemical alterations induced by the mixture were greater than those recorded for each of the individual insecticides. The joint action analysis, based on the obtained biochemical data, revealed the dominance of antagonistic action among MET and ABM. Zinc supplementation achieved noticeable ameliorative effects. It was concluded that zinc may act as a powerful antioxidant, especially in individuals who are occupationally exposed daily to low doses of such pesticides